Reduction in transforming growth factor beta receptor I expression and transcription factor CBFa1 on bone cells by glucocorticoid.
Glucocorticoid in excess suppresses bone formation in vivo and disrupts bone matrix protein synthesis by osteoblasts in vitro. In contrast, transforming growth factor beta (TGF-beta) potently enhances bone matrix apposition. The rat TGF-beta type I receptor gene promoter contains cis-acting elements for transcription factor CBFa1, which increases in parallel with osteoblast differentiation. Here we present molecular data linking these events. We show that previously unexplained effects of glucocorticoid on bone loss may be mediated in part by suppression of CBFa1, with a resultant decrease in the expression and activity of the TGF-beta type I receptor on matrix-producing bone cells.
Chang
D J
DJ
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA.
Ji
C
C
Kim
K K
KK
Casinghino
S
S
McCarthy
T L
TL
Centrella
M
M
D030201:Activin Receptors, Type I; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D050659:Core Binding Factor Alpha 1 Subunit; D003907:Dexamethasone / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000494:pharmacology*; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D005938:Glucocorticoids; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat